H2‐driven cofactor regeneration with NAD(P)+‐reducing hydrogenases

A large number of industrially relevant enzymes depend upon nicotinamide cofactors, which are too expensive to be added in stoichiometric amounts. Existing NAD(P)H‐recycling systems suffer from low activity, or the generation of side products. H2‐driven cofactor regeneration has the advantage of 100% atom efficiency and the use of H2 as a cheap reducing agent, in a world where sustainable energy carriers are increasingly attractive. The state of development of H2‐driven cofactor‐recycling systems and examples of their integration with enzyme reactions are summarized in this article. The O2‐tolerant NAD+‐reducing hydrogenase from Ralstonia eutropha is a particularly attractive candidate for this approach, and we therefore discuss its catalytic properties that are relevant for technical applications. Many industrially relevant enzymes depend upon expensive nicotinamide cofactors which must be recycled for enzyme applications to be economically viable. Here we review the state of development of H2‐driven enzymatic cofactor regeneration which has 100% atom efficiency and uses H2 as a cheap reducing agent. We show the O2 tolerant NAD+‐reducing hydrogenase from Ralstonia eutropha to be an attractive candidate.